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Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
Molecular Cytogenetics Book
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Molecular Cytogenetics Book

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The present book covers wide area of molecular biology and cytogenetic biology in a form especially suitable for graduate (PG) students and undergraduate students (UG). This book will widely help to …

The present book covers wide area of molecular biology and cytogenetic biology in a form especially suitable for graduate (PG) students and undergraduate students (UG). This book will widely help to students, teachers, academicians to aid the knowledge about the course and beyond the course related to the subject matter as given in the box. In this book, we begin by describing the history of molecular biology and cytogenetic biology. Further, we turn to the nucleic acid, types and its structure, replication, transcription, translation, DNA damage and repair mechanisms. The cytogenetics describes in the chapter 6 followed by sex determination, karyotyping , chromosomal disorder, human genome project and gene library. The chapter 10 has cancer biology, in which the role of proto-oncogenes and oncogenes, its conversion, cancer treatment, drugs and therapy is discussed. Finally, the chapter 11 includes the molecular evolution. Boxed material throughout the book is provided to illustrate the topics covered in the main text, explanations of the medical relevance and in depth sections that extend the coverage beyond the content of the main text.

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  • 1. A TEXT BOOK OF MOLECULARCYTOGENETICS
  • 2. A TEXT BOOK OF MOLECULAR CYTOGENETICS Ashok Kumar Assistant Professor Dept. of Biotecnology Himachal Institute of Life Science, Paonta Sahib – 173025 (Himachal Pradesh) India And Meena Srivastava Associate Professor Dept. of Zoology, Maharana Pratap Government (PG) College Hardoi – 241001 (Uttar Pradesh) IndiaNARENDRA PUBLISHING HOUSE DELHI-110006 (INDIA)
  • 3. Copyright © 2012, Narendra Publishing House, Delhi (India)All rights reserved. Neither this book nor any part may be reproduced or used inany form or by any means, electronic or mechanical, including photocopying,microfilming, recording, or information storage and retrieval system, without thewritten permission of the publisher and author.The information contained in this book has been obtained from authentic andreliable resources, but the authors/publisher cannot assume responsibility for thevalidity of all materials or the consequences of their use. The authors/ publisherhave attempted to trace and acknowledge the materials reproduced in thispublication and apologize if permission and acknowledgements to publish in thisform have not been given. If any material has not been acknowledged pleasewrite and let us know so we may rectify it.First Edition 2012ISBN: 978-93-80428-79-6Published by :NARENDRA PUBLISHING HOUSEPublisher and Distributor1417, Kishan Dutt Street, Maliwara,DELHI-110006 (India)Phones: 91-011-23268470, 91-011-23259412E-mail: info@nphindia.com Website: www.nphindia.comLaser Typeset by Amrit Graphics, Shahdara, Delhi 110 032Printed in India
  • 4. This Book is Dedicated to My Divine Mother “Smt. Kamla Devi” (Mummi)
  • 5. ContentsPreface xxiAcknowledgements xxiii1. MOLECULAR BIOLOGY ........................................................................ 1 Introduction ..................................................................................................... 1 Molecular Biology ........................................................................................... 5 Chromosomes and Inherited Traits ................................................................ 7 Discovery of Structure of DNA .................................................................... 8 Complementary Nucleotides ........................................................................... 8 Central Dogma ............................................................................................... 8 History of RNA Tertiary Structure ................................................................ 9 Crystal Structure of tRNA ............................................................................. 9 Hammerhead Ribozyme ............................................................................... 10 Protein ............................................................................................................11 Biotechnology ................................................................................................ 13 Development of Molecular Biology and Cytogenetics ................................ 16 Components of Molecular Biology ............................................................... 20 Restriction Enzymes ..................................................................................... 21 Restriction Endonucleases ..................................................................... 21 Type II Restriction Endonucleases ........................................................ 22 Isoschizomers ......................................................................................... 23 Restriction Mapping ............................................................................... 23 Host Cells ............................................................................................... 24 Nucleic Acid Hybridization ........................................................................... 24 Polymerase Chain Reaction ......................................................................... 25 Nucleic Acid Sequencing .............................................................................. 26 Nucleic Acids ................................................................................................ 27 Types of Nucleic Acids ................................................................................ 28 Ribonucleic Acid ........................................................................................... 28 Deoxyribonucleic Acid (DNA) ..................................................................... 29 Nucleic Acid Components ............................................................................ 29
  • 6. viii Nucleobases .................................................................................................. 29 Nucleosides ................................................................................................... 29 Nucleotides and Deoxynucleotides ............................................................... 30 History of Nucleic Acid ................................................................................ 30 Experimental Proof of the Genetic Function of DNA ................................ 31 Structure of DNA ......................................................................................... 34 Properties of DNA ....................................................................................... 35 Bases ...................................................................................................... 36 Base Pairing ........................................................................................... 39 Grooves ................................................................................................... 40 Sense and Antisense .............................................................................. 41 DNA Super Coiling ................................................................................ 41 Role of Supercoiling ............................................................................... 42 Occurrence of DNA super coiling ........................................................ 43 Alternate DNA Structures ........................................................................... 46 Quadruplex Structures .................................................................................. 47 B-DNA ......................................................................................................... 48 Branched DNA ............................................................................................. 49 A-DNA ......................................................................................................... 49 Z-DNA .......................................................................................................... 50 Biological Significance of Z DNA ......................................................... 51 Chemical Modifications of DNA ................................................................. 52 Base Modifications ................................................................................. 52 Biological Functions ................................................................................ 52 Genes and Genomes ..................................................................................... 52 Interactions with Proteins ............................................................................. 53 DNA-binding Proteins .................................................................................. 53 Watson and Crick Model of DNA ............................................................... 54 Features of the Watson-Crick base pair ............................................... 55 Features of the Watson-Crick model of B-DNA ................................. 56 Real Structure of B-DNA ............................................................................ 56 History of DNA Research ........................................................................... 57
  • 7. ixImportant Contributors to the Field of DNA ............................................... 57Ribonucleic Acid ........................................................................................... 61 Discovery of RNA ................................................................................. 63 Type of RNA ......................................................................................... 64 Ribosomal RNA (rRNA) ....................................................................... 64 Prokaryotes vs. Eukaryotes ................................................................... 64 Prokaryotes ............................................................................................. 65 Eukaryotes .............................................................................................. 65 Importance of rRNA ............................................................................. 65 Messenger RNA (mRNA) .................................................................... 66 Synthesis, Processing and Function ....................................................... 66 Transcription ........................................................................................... 66 Eukaryotic pre-mRNA Processing ........................................................ 66 5 cap addition ........................................................................................ 67 Splicing .................................................................................................... 67 Editing ..................................................................................................... 67 Polyadenylation ....................................................................................... 67 Transport ................................................................................................. 68 Translation ............................................................................................... 68Structure of mRNA ...................................................................................... 68 5 cap ...................................................................................................... 68 Coding regions ........................................................................................ 68 Untranslated regions .............................................................................. 69 Poly (A) tail ............................................................................................ 70 Monocistronic Versus Polycistronic mRNA .......................................... 70 mRNA Circularization ............................................................................ 70 Degradation ............................................................................................ 70 Prokaryotic mRNA Degredation ........................................................... 70 Eukaryotic mRNA Turnover .................................................................. 71 AU-rich Element Decay ........................................................................ 71 Nonsense Mediated Decay .................................................................... 71Small Interfering RNA (siRNA) .................................................................. 72
  • 8. x Micro RNA (miRNA) .................................................................................. 72 Small Nucleolar RNA (snRNA) .................................................................. 72 XIST RNA .................................................................................................... 73 Transfer RNA (tRNA) ................................................................................. 73 Secondary Structure of tRNA ............................................................... 73 3D Structure of tRNA ........................................................................... 75 Anticodon ................................................................................................ 76 Aminoacylation ....................................................................................... 76 Binding to Ribosome .............................................................................. 77 tRNA Genes ........................................................................................... 77 Formation and Processing ...................................................................... 77 Cellular Functions ................................................................................... 79 Gene Activation ...................................................................................... 79 Detecting and Manipulating miRNA Signaling ............................................ 80 miRNA and Disease ..................................................................................... 80 Similarities and Differences between DNA and RNA ............................... 81 Selfish DNA .................................................................................................. 82 Satellite DNA ............................................................................................... 82 Minisatellite DNA .................................................................................. 82 Microsatellites DNA .............................................................................. 83 Central Dogma of Molecular Biology .......................................................... 842. REPLICATION .......................................................................................... 88 DNA Replication-Some Facts ...................................................................... 88 DNA Polymerase ......................................................................................... 93 Helicases ....................................................................................................... 94 Structural Feature of Helicases ............................................................. 94 Superfamilies of Helicase ...................................................................... 94 Function of Helicase .............................................................................. 95 Origin of Replication ..................................................................................... 95 Types of Origin of Replication ............................................................... 96 Prokaryotic Origin of Replication .......................................................... 96 Eukaryotic Origin of Replication ............................................................ 97 Replication fork ............................................................................................. 98
  • 9. xi Leading strand synthesis ........................................................................ 98 Lagging strand synthesis ........................................................................ 98 Prokaryotic DNA Replication ..................................................................... 100 Initiation ................................................................................................ 100 Elongation ............................................................................................. 101 Termination ........................................................................................... 101 Eukaryotic DNA replication ....................................................................... 102 Regulation of Replication ..................................................................... 103 Termination of Replication ................................................................... 104 Rolling circle Replication ............................................................................ 105 Replication of Plasmids ........................................................................ 105 Control of Plasmid Replication and Copy-number .............................. 1063. TRANSCRIPTION ..................................................................................108 Introduction ................................................................................................. 108 RNA Polymerase I ..................................................................................... 108 Initiation ................................................................................................ 109 Elongation ............................................................................................. 109 Termination ............................................................................................ 110 RNA Polymerase II ..................................................................................... 110 Stages of Transcription ......................................................................... 110 Initiation ................................................................................................. 111 Initiation Regulation ............................................................................... 112 C-terminal Domain ................................................................................ 113 5’Capping ............................................................................................... 113 Spliceosome ........................................................................................... 113 RNA polymerase III .................................................................................... 113 Initiation ........................................................................................................ 114 Class I .................................................................................................... 114 Class II .................................................................................................. 114 Class III ................................................................................................. 114 Termination ............................................................................................ 115 Operon Concepts ......................................................................................... 115
  • 10. xii 1. Lac Operon ..................................................................................... 115 Lactose analogues .......................................................................... 118 Allolactose ....................................................................................... 119 b-galactosidase Activity .................................................................. 119 Mechanism of Induction ................................................................. 119 Application of lac Operon ............................................................. 120 2. Trp Operon ..................................................................................... 120 Repression ...................................................................................... 121 Attenuation ..................................................................................... 121 Eukaryotic Gene Regulation ................................................................ 123 Enzyme Regulation ............................................................................... 124 a. Genetic Control .............................................................................. 124 b. Controlling the enzyme’s activity (feedback inhibition) ................ 126 Post Transcriptional Modification ......................................................... 127 1. 5 caping ......................................................................................... 127 Capping Process ............................................................................ 127 5 Capping Targeting ...................................................................... 128 2. Polyadenylation .............................................................................. 129 Nuclear polyadenylation ................................................................ 129 Mechanism of Nuclear Poly ademylation ..................................... 130 a. Factor (Proteins involded) ....................................................... 130 b. Downstream Effects ............................................................... 131 c. Deadenylation .......................................................................... 131 3. Alternative Polyadenylation ........................................................... 131 Cytoplasmic Polyadenylation ......................................................... 132 Tagging for Degradation in Eukaryotes ........................................ 132 4. RNA splicing .................................................................................. 132 i) Splicing Mechanism ................................................................ 133 Beta-globin gene ..................................................................... 134 ii) Sex Lethal Gene ..................................................................... 134 5. RNA Editing ................................................................................... 136 Importance of RNA Editing .......................................................... 136
  • 11. xiii4. TRANSLATION .......................................................................................138 Introduction ................................................................................................. 138 Genetic Code .............................................................................................. 138 History of Genetic Code ...................................................................... 139 Transfer of Information via Genetic Code .......................................... 139 Salient Features of Genetic Code ........................................................ 142 Theories on the Origin of the Genetic Code ....................................... 145 Wobble Base Pair and Wobble Hypothesis ............................................... 146 Aminoacyl-tRNA ........................................................................................ 148 Translation in Prokaryotes .......................................................................... 150 Translation in Eukaryotes ........................................................................... 152 Posttranslational Modification ..................................................................... 153 Molecular chaperones and HSP .......................................................... 165 Molecular Chaperone ........................................................................... 165 Location and Functions ........................................................................ 165 Bacterial and Archeal Chaperones ...................................................... 166 Chaperonins .......................................................................................... 166 Categories of Chaperonins ................................................................... 167 Mechanism of Action ................................................................................. 167 Heat Shock Proteins (HSP) ....................................................................... 168 Classification ........................................................................................ 168 Function of Heat Shock Protein .......................................................... 169 Applications .......................................................................................... 170 Protein Processing ............................................................................... 171 Proteasomes ......................................................................................... 172 Structure and Organization .................................................................. 172 20S Core Particle ................................................................................. 173 19S Regulatory Particle ....................................................................... 174 Regulation of the 20S by 19S .............................................................. 174 11S regulatory particle ......................................................................... 174 Assembly .............................................................................................. 175 Ubiquitylation and Targeting ....................................................................... 175 Unfolding and Translocation ................................................................ 176 Proteolysis ............................................................................................. 177 Ubiquitin-independent Degradation ...................................................... 177
  • 12. xiv Cell Cycle Control ...................................................................................... 178 Regulation of Plant Growth ........................................................................ 178 Apoptosis ................................................................................................. 179 Response to Cellular Stress ........................................................................ 179 Proteasome Inhibitors ................................................................................. 1805. DNA DAMAGE AND REPAIR ............................................................181 DNA Repair ................................................................................................ 181 DNA Damage ............................................................................................. 181 Types of Damage ................................................................................. 182 Nuclear Versus Mitochondrial DNA Damage .................................... 183 Senescence and Apoptosis ......................................................................... 183 DNA Damage and Mutation ...................................................................... 184 Agents that Damage DNA ........................................................................ 184 DNA Repair Mechanisms .......................................................................... 185 Direct Reversal ........................................................................................... 186 Single Strand Damage ................................................................................ 186 1. DNA Mismatch Repair ........................................................................ 186 i) Mismatch Repair Proteins ............................................................. 188 a) MutS Homologs ...................................................................... 188 b) MutL Homologs ...................................................................... 189 c) MutH ....................................................................................... 189 d) b-sliding clamp ......................................................................... 189 ii) Defects in Mismatch Repair ......................................................... 190 2. Base Excision Repair ........................................................................... 190 i) Lesions Processed by BER .......................................................... 191 ii) Proteins for Base Excision Repair ................................................ 192 3. Nucleotide Excision Repair (NER) ...................................................... 193 Double-strand Breaks .......................................................................... 194 Translesion Synthesis ........................................................................... 195 DNA Damage Checkpoints ................................................................. 195 SOS Response ...................................................................................... 196 Eukaryotic Transcriptional Responses to DNA Damage ................... 197 DNA Repair and Evolution .................................................................. 197 Xeroderma Pigmentosum ..................................................................... 198
  • 13. xv i) Types of XP ................................................................................... 199 ii) Symptoms of XP ........................................................................... 199 iii) Treatment ....................................................................................... 200 Mutation ......................................................................................... 200 Mutagens ........................................................................................ 2016. CYTOGENETICS ....................................................................................202 Organization of DNA in chromosome ....................................................... 202 i) Introduction ........................................................................................... 202 ii) Chromosome Structure ........................................................................ 203 a) Chromatin ....................................................................................... 204 b) Packaging of DNA in Chromatin .................................................. 204 Interphase Chromatin ................................................................................. 205 Metaphase Chromatin and Division ........................................................... 205 Chromatin and Watson/Crick base Pairing ................................................ 206 Histone ........................................................................................................ 206 Nucleosome and Beads-on-a-string ........................................................... 207 Chromatin Fibre .......................................................................................... 209 DNA Superhelix .......................................................................................... 210 Spatial Organization of Chromatin ............................................................. 210 Nucleoid ....................................................................................................... 211 Circular Bacterial Chromosome .................................................................. 211 Structure of Eukaryotic Chromosome ........................................................ 212 Centromere ................................................................................................. 212 Centromere Positions .................................................................................. 212 Telomere ...................................................................................................... 213 Structure and Functions of Telomere ......................................................... 214 Number of Chromosomes .......................................................................... 215 i) Eukaryotes ............................................................................................ 215 ii) Prokaryotes ........................................................................................... 216 Heterochromatin ......................................................................................... 216 i) Constitutive Heterochromatin ............................................................... 217 ii) Facultative Heterochromatin ................................................................ 217 iii) Yeast Heterochromatin ........................................................................ 218
  • 14. xvi Gene Family ................................................................................................ 218 Interrupted Gene ......................................................................................... 219 Euchromatin ................................................................................................ 219 Function ....................................................................................................... 220 C-value Paradox ......................................................................................... 220 C-value Paradox History ............................................................................ 220 Polytene Chromosome ................................................................................ 222 Chromosome Puffs ..................................................................................... 223 Lampbrush Chromosomes .......................................................................... 224 Linkage ....................................................................................................... 224 Frequency of Recombination ............................................................... 225 Importance of Linkage ......................................................................... 225 Sex Linkage ................................................................................................ 225 Genes on the Sex Chromosomes ......................................................... 226 Genetic and Hereditary Disorders ....................................................... 227 Types of Genetic Disorders ........................................................................ 227 Genetic Linkage .......................................................................................... 227 Linkage Mapping ........................................................................................ 228 Linkage Map ............................................................................................... 229 LOD Score Method .................................................................................... 230 Recombination Frequency .......................................................................... 230 Back cross .................................................................................................. 232 Test Cross ................................................................................................... 233 Two Point Test Cross ................................................................................. 234 Chi square Analysis for Linkage ................................................................ 237 Map Distance .............................................................................................. 238 Hardy-Weinberg Equilibrium ...................................................................... 239 Random Mating .......................................................................................... 2397. SEX DETERMINATION .......................................................................244 Indroduction ................................................................................................. 244 Sex Determination in Mammal ................................................................... 244 Sex Determination Mechanisms .......................................................... 245 Primary Sex Determination .................................................................. 245 Secondary Sex Determination ............................................................. 246
  • 15. xvii Testis Determining Factor (TDS) ............................................................... 246 Function of SRY ......................................................................................... 247 Role of SOX9 ............................................................................................. 248 Female Development .................................................................................. 248 Gonadal Sex ................................................................................................ 249 Fetal Production of Gonadal Hormones .................................................... 249 External Genitalia ........................................................................................ 249 Chromosomal Sex Determination (CSD) ............................................ 250 Environmental Sex Determination (ESD) ........................................... 250 Sex Determination System in Insects ........................................................ 251 Sex chromosomes in Insects ...................................................................... 254 ZW Sex Chromosomes .............................................................................. 255 Haplodiploidy ............................................................................................... 255 Non genetic Sex determination Systems ................................................... 256 Sex Determination Mechanisms in Insects ................................................ 256 Comparison of Sex Determination System ................................................ 257 Dosage Compensation ................................................................................ 259 Barr Bodies ................................................................................................. 2628. KARYOTYPING AND CHROMOSOMAL DISORDERS ..............264 Human Chromosomes ................................................................................ 264 Gene Complexity ........................................................................................ 266 Single Nucleotide Polymorphisms ............................................................... 267 Chromosomes in Eukaryotes ...................................................................... 267 Chromosomes in Prokaryotes ..................................................................... 267 Karyotype .................................................................................................... 268 History of Karyotype Studies .............................................................. 270 Observations on karyotypes ................................................................. 270 Human Karyotype ................................................................................ 271 Diversity and Evolution of Karyotypes ............................................... 272 i) X inactivation ................................................................................. 272 ii) Number of Chromosomes in a Set ............................................... 272 iii) Fundamental Number .................................................................... 273 iv) Ploidy .............................................................................................. 273
  • 16. xviii v) Aneuploidy ..................................................................................... 274 vi) Chromosomal Polymorphism ......................................................... 274 Karyotyping ................................................................................................. 274 i) Classic Karyotype Cytogenetics ................................................... 274 ii) Spectral karyotype (SKY Technique) ........................................... 275 iii) Digital Karyotyping ........................................................................ 275 Chromosome Abnormalities ........................................................................ 276 Chromosomal Banding ................................................................................ 277 Types of Banding ........................................................................................ 278 Staining Protocols ....................................................................................... 279 i) Protocol-1: Giemsa Staining ................................................................. 279 ii) Protocol-2: Leishman’s Stain ............................................................... 280 iii) Protocol-3: G-Banding .......................................................................... 281 iv) Protocol-4: C-Banding .......................................................................... 282 v) Protocol-5: Giemsa Reverse Banding (RHG) ..................................... 284 vi) Protocol-6: R Banding by Fluorescence using vii) Protocol-7: T-Banding .......................................................................... 286 Chromosomal Aberrations .................................................................... 287 Genetic and Hereditary Disorders ....................................................... 288 Types of Genetic Disorders ................................................................. 288 1. Single Gene Disorders ................................................................... 290 2. Multifactorial and Polygenic Disorders ......................................... 300 3. Disorders with Variable Modes of Transmission .......................... 301 4. Cytogenetic Disorders ................................................................... 3019. HUMAN GENOME PROJECT AND GENE LIBRARY ................302 Human Genome Project ............................................................................. 302 Indroduction .......................................................................................... 302 Complation of Human Genome project ............................................... 304 Findings ................................................................................................. 306 Ethical, Legal and Social Issues .......................................................... 306 Concerns of the Sequencing Project ................................................... 307 Public Versus Private Approaches ...................................................... 308 Advantages of Human Genome Project ............................................. 309 Benefits of Human Genome Project ................................................... 309
  • 17. xix Genotype ..................................................................................................... 310 Gene Library ................................................................................................ 311 Principle of Gene Cloning ..................................................................... 311 Basic Steps ........................................................................................... 312 Genomic Library .................................................................................. 315 i) Constructing Genomic Libraries using Plasmids ................................. 316 Types of Vectors .................................................................................. 316 Steps: .................................................................................................... 316 ii) Constructing Genomic Libraries using Bacteriophage Vectors .......... 318 iii) Constructing Genomic Libraries with Yeast Artificial Chromosomes ....................................................................................... 320 Applications of Genomic Libraries ...................................................... 320 cDNA Library ............................................................................................. 321 Construction of Library ........................................................................ 322 Uses of cDNA Library ........................................................................ 32510. CANCER BIOLOGY ..............................................................................326 Introduction ................................................................................................. 326 Historical Perspective ................................................................................. 327 Classification of Cancer ....................................................................... 330 Signs and Symptoms ............................................................................ 331 Causes of Cancer ....................................................................................... 331 Mechanism of Cancer ................................................................................ 335 Epigenetics ............................................................................................ 336 Oncogenes ............................................................................................ 337 Proto-oncogene .................................................................................... 338 Activation .............................................................................................. 338 Conversion of Proto-oncogenes ................................................................. 338 Tumor Suppressor Genes ..................................................................... 339 Protein 53 ............................................................................................. 340 Structure of p53 ................................................................................... 341 Significance of p53 ............................................................................... 342 Regulation of p53 Activity ................................................................... 342 Role in Disease .................................................................................... 343 Biological Properties of Cancer Cells ........................................................ 344
  • 18. xx Comparison to Non-biological Organisms .................................................. 345 Prevention of Cancer ................................................................................. 345 Diagnosis .............................................................................................. 348 Treatment .............................................................................................. 349 Control of Symptom ............................................................................. 35111. MOLECULAR EVOLUTION ..............................................................354 Beginning of Life ........................................................................................ 354 RNA World ................................................................................................. 356 DNA World ................................................................................................. 357 Phylogenetic Analysis ................................................................................. 358 Evolution of Eukaryotic Cells ..................................................................... 358 GLOSSARY ...............................................................................................361 SUBJECT INDEX ...................................................................................376LIST OF BOX 1. Molecule ................................................................................................. 16 2. Nucleosides, Phosphate and Nucleotides .............................................. 34 3. X-ray crystallography and Watson and Crick ....................................... 60 4. Ubiquitin ................................................................................................ 160 5. Genetic Sex .......................................................................................... 249 6. History of Sex Determination in Insects ............................................. 251 7. Sex Determination in Amphibian ......................................................... 258 8. Genetic Characters Due to Chromosomal Abnormalitiy ..................... 289 9. Important Terms of Cancer Biology .................................................... 329
  • 19. PrefaceT he present book entitled A Text Book of “Molecular Cytogenetics” aims to cover a wide area of molecular biology and cytogenetic biology in a form especially suitable for graduate (PG) and undergraduate students(UG). We have deliberately kept the book to a manageable size so that neitherthe cost and content nor the weight is too overwhelming for the student. Thisbook will widely help to students, teachers, academicians to aid the knowledgeabout the course and beyond the course related to the subject matter as givenin the box. Present book contains 11 chapters. We begin by describing the historyof molecular and cytogenetic biology. Further, we turn to the nucleic acid, typesand its structure. The chapter 2 describes replication of DNA and enzymology,chapter 3 dscribes the transcription and modification and translation of protein isdiscussed in chapter 4. The next chapter 5 has DNA damage and repairmechanisms. The cytogenetics describes in the chapter 6 and sex determinationand differentiation is discussed in chapter 7. The chapter 8 has karyotyping andchromosomal disorder, chapter 9 has human genome project and gene library.The chapter 10 has cancer biology, in which the role of proto-oncogenes andoncogenes, its conversion, cancer treatment, drugs and therapy is discussed.Finally, the chapter 11 includes the molecular evolution. Boxed material throughoutthe book is divided into examples to illustrate the topics covered in the main text,explanations of the medical relevance of the material and in depth sections thatextend the coverage beyond the content of the main text. Ashok Kumar (Email: asokumr@gmail.com) Meena Srivastava (Email: meena.zoology@gmail.com)
  • 20. Acknowledgements By the grace of almighty, we have reached this opportunity to thank all those who have been instrumental in bringing this book to completion.I t’s our immense pleasure to thank Dr. Ramanand Prasad, Director Higher Education, Uttar Pradesh (India) for motivation to write this manuscript. We express our sincere gratitude to Dr. D.K. Singh, Principal, M.P. Govt. (PG)College, Hardoi (UP) India, Prof. N. Singh Dept. of Biotechnology and Zoology,Prof. S.C. Tiwari and Prof. J.P. Mehta, Dept. of Microbiology and BotanyHNBGU (A Central University), Srinagar-Garhwal (Uttarakhand), India for theircritical suggestions and inspirations. Our special thanks to Prof. B.S. Bisht, Dept.of Zoology, HNBGU (A Central University), SRT Campus Badshahithaul Tehri(Uttarakhand) India, Dr. D. K. Srivastava, Principal, Govt PG College, Rajajipuram,Lucknow (India), Dr. I.D. Singh, Ex Head, Dept. of Botany, M. P. Govt (PG)College Hardoi (UP) India, Dr. V.D. Joshi, Principal, Govt PG College Purola,Uttarkashi (Uttarakhand) India, Dr. Arun Bhatt, Dr. Harish Chandra and Dr.Manoj Bhatt, Dept. of Biotechnology, G.B. Pant Engineering College Pauri-Garhwal,Dr. Arun Kumar, Director Research, Dolphin Institute of Biomedical and NaturalSciences, Dr. A.K. Singh, Scientist E, Wadia Institute of Himalayan Geology,Dehradun, Dr. S.P. Goyal, Scientist F and Head, Forensic Science Laboratory,Wild Life Institute of India, Dehradun, Er. P. Dwivedi Dept. of Biothchnology,Amity Institute Noida, India, Dr. Saswat Katiyar Dept. of Biochemistry, CSJMUKanpur (UP) India, Dr. Sandip Kumar and Dr. Sandip Tripathi, NIMS UniversityJaipur India, Dr. Ashish Thapliyal, Scientist State Biotech Program Utterakhand,Prof. U.K. Atheya, Dr. N. Rai Dept. of Biotech, GEU Dehradun, Dr. AftabAhmad, Director Beehive College Dehradun, Dr. G. Sunil Babu, Dept. of Env.Biothech BRA University Lucknow (U.P.), Dr. M.S. Khan, Dept. of MicrobiologyAMU. Aligarh, Dr. A. K. Chopra, Dr. P.C. Joshi, Dept. of Zoology, GurukulKangari University Haridwar, Dr. R. Kumar, Scientist, IARI Delhi, Dr. SanjayGupta Dept. of Biotech, SBS College Dehradun, for discussions and valuablecomments which have helped to improve the matter.
  • 21. xxiv We thank our colleagues Drs. Kiran Yadav, Archana Rajan, Anju Agarwal,Sangeeta Awasthi, V.L. Saxena, V.K. Dhatwalia, Pankaj Dhiman, Dinesh Kumarand Navneet Kumar and for their scientific discussions and valuable company tokeep cheerful and focused. We sincerely appreciate the help and support renderedby Mrs. Kanchan Prabha Rathoure, Er. Jitendra Kumar and Mr. Atul KumarSingh. Our sincere thanks to all other friends and colleagues whose names wehave not mentioned here for want of space. Thank you all forever!!! Authors

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